1js6

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(New page: 200px<br /><applet load="1js6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1js6, resolution 2.60&Aring;" /> '''Crystal Structure of...)
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[[Image:1js6.gif|left|200px]]<br /><applet load="1js6" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1js6, resolution 2.60&Aring;" />
caption="1js6, resolution 2.60&Aring;" />
'''Crystal Structure of DOPA decarboxylase'''<br />
'''Crystal Structure of DOPA decarboxylase'''<br />
==Overview==
==Overview==
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DOPA decarboxylase (DDC) is responsible for the synthesis of the key, neurotransmitters dopamine and serotonin via decarboxylation of, L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively. DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension. Peripheral inhibitors of, DDC are currently used to treat these diseases. We present the crystal, structures of ligand-free DDC and its complex with the anti-Parkinson drug, carbiDOPA. The inhibitor is bound to the enzyme by forming a hydrazone, linkage with the cofactor, and its catechol ring is deeply buried in the, active site cleft. The structures provide the molecular basis for the, development of new inhibitors of DDC with better pharmacological, characteristics.
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DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters dopamine and serotonin via decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively. DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension. Peripheral inhibitors of DDC are currently used to treat these diseases. We present the crystal structures of ligand-free DDC and its complex with the anti-Parkinson drug carbiDOPA. The inhibitor is bound to the enzyme by forming a hydrazone linkage with the cofactor, and its catechol ring is deeply buried in the active site cleft. The structures provide the molecular basis for the development of new inhibitors of DDC with better pharmacological characteristics.
==About this Structure==
==About this Structure==
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1JS6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with PLP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Aromatic-L-amino-acid_decarboxylase Aromatic-L-amino-acid decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.28 4.1.1.28] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JS6 OCA].
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1JS6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Aromatic-L-amino-acid_decarboxylase Aromatic-L-amino-acid decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.28 4.1.1.28] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JS6 OCA].
==Reference==
==Reference==
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[[Category: Burkhard, P.]]
[[Category: Burkhard, P.]]
[[Category: Dominici, P.]]
[[Category: Dominici, P.]]
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[[Category: Jansonius, J.N.]]
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[[Category: Jansonius, J N.]]
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[[Category: Malashkevich, V.N.]]
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[[Category: Malashkevich, V N.]]
[[Category: PLP]]
[[Category: PLP]]
[[Category: carbidopa]]
[[Category: carbidopa]]
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[[Category: vitamin b6]]
[[Category: vitamin b6]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:32:19 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:26:09 2008''

Revision as of 11:26, 21 February 2008


1js6, resolution 2.60Å

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Crystal Structure of DOPA decarboxylase

Overview

DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters dopamine and serotonin via decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively. DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension. Peripheral inhibitors of DDC are currently used to treat these diseases. We present the crystal structures of ligand-free DDC and its complex with the anti-Parkinson drug carbiDOPA. The inhibitor is bound to the enzyme by forming a hydrazone linkage with the cofactor, and its catechol ring is deeply buried in the active site cleft. The structures provide the molecular basis for the development of new inhibitors of DDC with better pharmacological characteristics.

About this Structure

1JS6 is a Single protein structure of sequence from Sus scrofa with as ligand. Active as Aromatic-L-amino-acid decarboxylase, with EC number 4.1.1.28 Full crystallographic information is available from OCA.

Reference

Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase., Burkhard P, Dominici P, Borri-Voltattorni C, Jansonius JN, Malashkevich VN, Nat Struct Biol. 2001 Nov;8(11):963-7. PMID:11685243

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